PubMed HealthSearch

Biomedical subjects

H Stricker

Publications and source records attributed to H Stricker.

18 recordsLinked to original sources

Functional characterization of a variant factor XII (F XII Locarno) in a cross reacting material positive F XII deficient plasma.

The plasma of a healthy woman was found to contain half normal factor XII (FXII) antigen level (0.46 U/ml) without any FXII clotting activity (less than 0.01 U/ml). The variant FXII in this plasma, denoted as FXII Locarno, was partially characterized by immunological and functional studies on the proposita's plasma. FXII Locarno is a single chain molecule with the same size (Mr = 80 kDa) as normal FXII. Isoelectric focusing suggested an excess of negative charge in the variant FXII as compared to normal FXII. In contrast to FXII in normal plasma, FXII Locarno was not proteolytically cleaved upon prolonged incubation of proposita's plasma with dextran sulfate. Adsorption to kaolin was similar for both, abnormal and normal FXII. Incubation of the proposita's plasma with dextran sulfate and exogenous plasma kallikrein showed normal cleavage of FXII Locarno outside of the tentative disulfide loop Cys340-Cys467, but only partial cleavage within this disulfide loop. Furthermore, plasma kallikrein-cleaved abnormal FXII showed neither amidolytic activity nor proteolytic activity against factor XI and plasma prekallikrein. These results suggest a structural alteration of FXII Locarno, affecting the plasma kallikrein cleavage site Arg353-Val354 and thus formation of activated FXII (alpha-FXIIa).

Amides

[Severe accidental hypothermia with cardiopulmonary arrest: prolonged resuscitation without extracorporeal circulation].

We describe a case of severe hypothermia in a 32-year-old patient who fell into a crevasse. Three hours later he was rescued and flown to a district hospital. On arrival he was apparently dead, with cadaveric skin, dilated and fixed pupils, pulseless and in respiratory arrest. His rectal temperature was 26 degrees C. On the ECG monitor there was first ventricular fibrillation, then, after several unsuccessful attempts at defibrillation, the heart became asystolic. Cardiopulmonary resuscitation was begun with orotracheal intubation and external cardiac compression, which eventually lasted 4 hours and continuously required a team of 6 persons. Only at a temperature of 32.5 degrees C could the patient be defibrillated with success. In the absence of extracorporeal circulation (ECC) the victim was rewarmed by warm-air breathing and by instillation of warm saline in peritoneum, stomach and bladder. In this way the rewarming velocity was 1.8 degrees C/hour. The postacute course was characterized by severe rhabdomyolysis (CK of 100,000 U/L) with non-oliguric renal failure, which necessitated several sessions of hemodialysis. Four months later the asymptomatic patient returned to work. Our case shows that a severely hypothermic patient can successfully be treated in a primary hospital not equipped with an ECC, provided that there is a sufficiently large team. Further, uninterrupted external cardiac compression guarantees efficient circulation even over several hours. Electric defibrillation in a hypothermic patient is ineffective unless normal body temperature has been reached. Lastly, every effort to continue resuscitation must be made in the still hypothermic patient whose absence of clinical response may obscure the real possibility of complete recovery.

Adult

Intraneoplastic application of metrizamide-containing liposomes: kinetic studies with computed tomography.

Liposomes may serve as drug carriers not only for systemic chemotherapy but also for intraneoplastic drug therapy because they show a sustained drug release. In the present study, the in vivo kinetics of intraneoplastic deposits of large multilamellar vesicles containing metrizamide was followed up in a rat tumor model with computed tomography. The influence of four different lipid compositions on the retardation capacity of large multilamellar liposomes was investigated. By comparing the dynamic data of X-ray attenuation and volume of liposome deposits, a rank order for the in vivo stability of metrizamide containing multilamellar vesicles could be established: the least stable liposomes were made of pure dimyristoyl-phosphatidyl-choline, the most stable type was made of equimolar parts of stearoyl-palmitoyl-phosphatidyl-choline and cholesterol. Of intermediate stability were liposomes made of equimolar parts of dimyristoyl-phosphatidyl-choline and cholesterol, and those made of pure stearoyl-palmitoyl-phosphatidyl-choline. The addition of 50% cholesterol increased the membrane stability of both dimyristoyl-phosphatidyl-choline and stearoyl-palmitoyl-phosphatidyl-choline liposomes. No diffusion of large multilamellar liposomes away from the injection site was observed. The in vivo stability of the liposomes was considerably less than that observed in vitro, suggesting active degradation processes. It is concluded that large, multilamellar liposomes may be suitable carriers for intraneoplastic chemotherapy. The present model is easily adaptable to be transferred into clinical conditions, and may allow direct monitoring of intraneoplastic liposome-mediated chemotherapy in human brain tumors.

Animals

[Diagnosis of deep venous thrombosis].

The clinical diagnosis of deep venous thrombosis (DVT) is unreliable. Phlebography, an invasive method, has gained wide diffusion and is considered as gold standard, but it has several draw-backs such as elevated costs and x-ray exposure. For these reasons, other, non-invasive techniques for diagnosing DVT have been looked for. Among them, CW-Doppler, occlusion plethysmography and, more recently, colour-Duplex-sonography have gained most acceptance. While the first two methods are able to diagnose with sufficient sensitivity and specificity proximal DVT, they are unreliable for isolated calf vein thrombosis. The colour-Duplex-sonography, on the other hand, produces results similar to phlebography for proximal thrombosis and succeeds in detecting isolated calf vein thrombosis with sufficient accuracy. We propose therefore the following non-invasive proceeding when confronted with the question of DVT: The first investigation to be done is a (colour)-Duplex examination. If one lacks such an infrastructure, an investigation with CW-Doppler or occlusion plethysmography has to be performed. If the results are positive, the patient will be treated. Otherwise, the exam will be repeated after five to seven days for CW-Doppler and plethysmography. If now the result is positive, the patient will be treated, otherwise, as with a negative Duplex study, the suspicion of DVT will be dismissed.

Blood Flow Velocity

Bioequivalence studies: single vs multiple dose.

Bioequivalence of different preparations of the same drug substance has gained considerable importance over the last few years due to increasing generic substitution. The procedure that the manufacturer of the generic test preparation has to show bioequivalence with an appropriate reference preparation is scientifically accepted and laid down in international regulations. However, the necessity of single- vs multiple-dose bioequivalence studies has not been discussed in detail with the exception of the Dutch and US guidelines on sustained-release theophylline formulations, where multiple-dose studies are specifically required. This paper compares the conclusions drawn from single- and multiple-dose studies in the same subjects and recommends appropriate pharmacokinetic characteristics.

Chemistry, Pharmaceutical

Tumour targeting with antibody-coupled liposomes: failure to achieve accumulation in xenografts and spontaneous liver metastases.

The potential of small unilamellar liposomes coupled to anti-tumour monoclonal antibodies (immunoliposomes) to accumulate in solid tumour tissue was tested in two systems, i.e. a human malignant melanoma xenografted into nude mice and a syngeneic murine lymphoma ESb.Mp exhibiting spontaneous metastasis to the liver. Both monoclonal antibodies tested were partly released from immunoliposomes within a few hours, thus generating a seemingly constant level of circulating antibody. Nevertheless it was possible to follow the biodistribution of intact immunoliposomes by virtue of a radioiodine label incorporated into the lipid moiety. It was found that in both tumor systems, though they differed with respect to the size of lesions and maybe also to the vascular architecture of surrounding tissue, immunoliposome uptake was virtually nil. The blockade of uptake into solid tumour tissue was caused by the limited availability of immunoliposomes due to their moderate stability, but especially by the inability of the particulate carrier to extravasate.

Animals

Interstitial chemotherapy of experimental gliomas.

Two new approaches of interstitial (intratumoral) chemotherapy of gliomas are presented. Using s.c.-transplanted rat gliomas (G616) the therapeutic activity of biologically degradable polylactide rods as carriers for methotrexate was investigated. Carrier-mediated intratumoral chemotherapy was superior both to a systemic treatment and an intratumoral treatment with the free drug. The activity of the alkyllysophospholipids Et-18-OCH3 and BM 41.440 and of the alkylphosphocholine He-PC was investigated in a human glioma xenograft (T 406). All three compounds were highly active following intratumoral administration.

Animals

[Peripheral arterial complications of various catheter angiography methods].

Between 1980 and 1988 12,251 arterial punctures for cardiac catheterization (CC), percutaneous transluminal angioplasty (PTA), or pure diagnostic intraarterial angiography (IAA) have been performed in our clinics. 54 (0.44%), 39 (0.63%, CC), 12 (0.67%, PTA), 3 (0.07%, IAA) patients suffered from a complication at the site of the arterial puncture necessitating surgical correction. Adults developed false aneurysms or large hematomas whereas children tended to show thrombotic arterial occlusions. Generally the surgical procedures of these complications proved to be quite simple (over two thirds) but some, especially in children, turned out to be more difficult. 3 arterial spasms in children and 1 prolonged wound healing in the groin, all without long-term sequelae and 1 severe graft infection necessitating ligation of the common femoral artery with severe ischemic signs for several months were the only complications of our corrective surgical procedures. We therefore plead for these iatrogenic complications of arterial puncture for an early correction performed by a surgeon with at least some experience in vascular surgery.

Adolescent

[Rare vascular complications of Behçet's disease (so-called angiobehçet)].

Vascular involvement in Behçet's disease is rare and may cause life-threatening complications. We report on 3 patients who presented with vascular problems in the course of the illness. (1) A 37-year-old woman suffered multiple pulmonary artery aneurysms (PAA) 3 years after the first symptoms of Behçet's disease (BD) had been noted. They completely regressed under three-month high-dose corticosteroid therapy and remission has lasted now for 2 years. (2) The second patient, a 22-year-old man, developed 2 vascular complications of BD: first (1986-1987), he was shown to have a sinus venous thrombosis which resolved under prednisone and oral anticoagulation therapy. Then (1988) he presented with multiple large PAA and high fever. Despite marked radiological regression of the multiple PAA under high-dose prednisone treatment, he remained symptomatic. Repeated hemoptysis in September 1988 prompted us to add cyclosporine A in a dosage providing whole blood levels of 250-350 ng/ml. Four months later pulmonary radiological studies had normalized, but manifestations of BD on the skin and mucosa remained unchanged. 7 months after starting Cy A therapy the patient died suddenly of massive hemoptysis. (3) The third patient, a 23-year-old Spanish immigrant, had a diagnosis of BD when presenting with sinus thrombosis. Later he underwent surgery 3 times for false aneurysms of the common femoral artery which developed at the site where he had been punctured for angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Multiple, large aneurysms of pulmonary arteries in Behçet's disease. Clinical remission and radiologic resolution after corticosteroid therapy.

We describe the case of a young European woman with Behçet's disease, hemoptysis, and multiple, large aneurysms of pulmonary arteries as confirmed by computed tomographic scan and angiography. Complete resolution of hemoptysis and radiologic signs of pulmonary artery aneurysms was observed three months after prednisone treatment, and a persisting remission was noted after ten months. We reviewed the literature on this rare complication and described the therapeutic approaches.

Adult

Bioequivalence studies: single vs multiple dose.

Bioequivalence of different preparations of the same drug substance has gained considerable importance over the last few years due to increasing generic substitution. The procedure that the manufacturer of the generic test preparation has to show bioequivalence with an appropriate reference preparation is scientifically accepted and laid down in international regulations. However, the necessity of single- vs multiple-dose bioequivalence studies has not been discussed in detail with the exception of the Dutch and US guidelines on sustained-release theophylline formulations, where multiple-dose studies are specifically required. This paper compares the conclusions drawn from single- and multiple-dose studies in the same subjects and recommends appropriate pharmacokinetic characteristics.

Adult

In vitro release and depot effect after intratumoral application of metrizamide-containing liposomes.

The drug release and intratumoral residence time of small and large liposomes composed of saturated phospholipids and cholesterol were measured in vitro and in tumor-bearing rats by computed tomography. The in vitro release of metrizamide at 37 degrees C was higher in tissue fluid than in diluted serum and PBS-buffer. The extent of release was 20%/48 h for the 100 nm-liposomes and 10%/48 h for the 480 nm liposomes. The decrease of x-ray contrast after intratumoral application resulted in a half-life of t50 = 0.05 d for metrizamide solution and t50 = 0.42 d for small liposomes. Large liposomes showed a linear decrease in contrast, the half-life being t50 = 15 d. While small liposomes rapidly leave the tumor, large liposomes rest intact in the tumor for about 30 d. Therefore they fulfill a fundamental prerequisite for intratumoral depots of cytostatics with controlled release.

Animals

Stability in biological fluids and clearance of immunoliposomes.

The in vivo and in vitro stability of liposomes having covalently bound monoclonal antibodies (MAB) connected to their surface via a disulfide bridge (about 6 anti-melanoma MAB-molecules per liposome) in tissue fluids was investigated. These immunoliposomes were composed of equimolar amounts of hydrogenated soybean lecithin and cholesterol and had a mean diameter of 113 nm. The protein-lipid binding, change of vesicle size and the release of encapsulated carboxyfluorescein (CF) were estimated. After i.v. injection into mice, an initial protein cleavage of 21% occurred within 30 min p.a., followed by a slow elimination of intact MAB-liposomes from blood circulation (t50 = 2.2 h). These liposomes had a similar elimination rate as protein-free liposomes. The in vitro results after incubation of MAB-liposomes in blood, plasma, serum and tissue fluid were very similar with regard to the protein-lipid cleavage, but the time dependence was different. The CF-release in vitro was slower (about 1.5%/d) than the protein cleavage; the vesicle size of MAB-liposomes increased substantially in contrast to protein-free liposomes in serum during 4 days.

Animals

[CT kinetics of intratumor liposome deposits].

CT follow-up studies of liposome-entrapped metrizamide after intraneoplastic injection into neurogenic s.c. rat tumors were performed. By closely resembling clinical examination conditions, the experimental design has proven suitable in determining the in vivo kinetics of these interstitial liposome deposits. When compared to free metrizamide which may be considered an analogue of water-soluble chemotherapeutics, the encapsulation of metrizamide in liposomes resulted in a retarded decline of the contrast enhancement. Diffusion of liposomes could not be detected and the X-ray attenuation values measured within the liposome deposits continuously decreased with time for both types of liposomes. In the case of multilamellar vesicles, this significantly corresponded to a zero order kinetics with a mean halflife of 300 h. An initial increment in the X-ray attenuation of the liposome deposits might be due to the interstitial absorption of the water component of the liposome-dispersion. Because of the pronounced retardation effect of multilamellar liposomes resulting in a 140-fold prolongation of the interstitial retention time of metrizamide and due to their release kinetics these vesicles may be an appropriate carrier system for a local interstitial chemotherapy modality. Small unilamellar vesicles having an interstitial half-life of 14 h may be used as a faster component of a composed therapy system.

Animals

[Concrete approaches to the promotion of prevention. Health education in schools].

Society nowadays entrusts the school with formative tasks which earlier were exclusively the role of the family unit. Numerous such tasks are in relation with the integration of the individual in society. As they usually concern attitudes and behaviors which the youth must actively adopt for themselves (get impregnated with), the school cannot limit its action to transmitting knowledge. This is true in particular for health education. Good mental health of the students is the precondition of a positive attitude vis-à-vis physical wellbeing. It is important therefore to give adequate emphasis to mental health requirements in teacher training.

Adult

[Improving the effectiveness of health education].

Discussions concentrated on ways of influencing the behavior of healthy individuals. The following was concluded; 1. Health education is an interdisciplinary activity. It should not merely be aimed at the behavior of individuals but also respect and influence values and institutions of society as well as legislation. 2. Family and school are the most important fields of activity. 3. Health education should be based on experiences from communication sciences. 4. In school, health education should be integrated in as many subjects as possible. Of special importance are the example of the teachers and adequate preparation and training. 5. Health education cannot limit itself to giving information, it also must motivate to a healthy way of life. 6. Exchange of experiences and information in health education should be improved. In Switzerland this can be done by a working party of the Swiss Society for Social and Preventive Medicine. 7. The intervention trials of the Swiss National Research Program can provide important stimuli for innovative approaches to health education is Switzerland.

Adult